Electrochemical deposition of bone

ABSTRACT

A method of improving orthopedic implant materials by the simultaneous electrodeposition of bone and collagen onto a prosthesis is provided. Collagen fibrils are dispensed in a gelatin medium and the gelled collagen is dissolved in a waterglycerine solution. Finely divided bone particles are then added to this solution and, by applying a voltage to a pair of electrodes immersed in the solution, adherent bone and collagen coatings of preferably 1-5 mils thickness are formed on the cathodic electrode.

Phillips et al. July 1, 1975 [54] ELECTROCHEMICAL DEPOSITION OF 3,443,261 5/1969 Battista et al. 3/1 BONE 3,556,969 1/1971 Mizuguchi et al. r 3,790,507 2/1974 l-lodosh 128/92 C X [75] Inventors: David C. Phillips, Pittsburgh; Bevil Shaw Murrysvine both of Primary Examiner-John H. Mack [73] Assignee: The United States of America as Assistant Examiner-{\- Prescot? represented by the Secretary of the Attorney, Agent, or FzrmR. S. Sclascla; C. E. Navy, Washington, DC vautram [22] Filed: Apr. 16, 1974 [57] ABSTRACT I [21] Appl- 461,470 A method of improving orthopedic implant materials by the simultaneous electrodeposition of bone and 52 us. Cl 1. 204/181; 3/1.9; 128/92 c; collagen Onto a Prosthesis is Provided Collagen fibrils 2 92 1 204 130 R are dispensed in a gelatin medium and the gelled col- [51] Int. Cl C23h 13/00 lagen is dissolved in a waterglycerine Solution Finely [58] Field f Search u 204/180 R, 181, 29 3 divided bone particles are then added to this solution 3/1.9 1 913; 128/92 C, 92 CA, 92 D and, by applying a voltage to a pair of electrodes immersed in the solution, adherent bone and collagen 5 References Cited coatings of preferably 1-5 mils thickness are formed UNITED STATES PATENTS 8/1959 Metcalfe et a1 204/18l on the cathodic electrode.

8 Claims, N0 Drawings ELECTROCHEMICAL DEPOSITION OF BONE The present invention concerns the improvement of orthopedic implant materials and, more particularly, the cathodic formation of bonecoatings on prostheses by electrodeposition thereon of finely divided bone particles.

Attempts to understand and correct the failures of orthopedic implants have revealed that such failures apparently are caused by fatigue, over-stressing, stress corrosion, etc., among other causes, and that many desirably strong materials are unsuitable because they are either directly or indirectly toxic to the host. One of the most difficult areas of orthopedic replacement is in the femur head where the stresses have been estimated to be up to four times the weight of the body. This area is one of the most common points of failure in the human body and, consequently, an urgent need exists for a sturdy and durable prosthesis for use therein. Another area in which total replacement of bone is necessary is that of damage from gunshot wounds. Here, since the bone does not appear to always grow along the prosthesis filling the gap, only occasional success has been achieved.

Some metallic implants such as the cobaltchromium-molybdenum alloy Vitallium have proved to be generally satisfactory, exhibiting the additional advantage of case-hardening with use. Such metallic implants reduce to a minimum the mechanical wearing problem which occurs between the replacement of the hipcup, or acetabulum, and the femur head prosthesis. The high density polyethylene which may be used as a lubricant between these working parts provides for a low wearing rate, a resistance to creep, and an absence of toxic effect. However, there are disadvantages to the use of such material for this kind of metallic prosthetic device since both 316 stainless steel and cobaltchromium-molybdenum implants may be carcinogenic in rats. There are also disadvantages to the use of methylmethyacrylate as a bearing material in the acetabulum since methylmethacrylate deteriorates in the human body. There is thus an unfilled need for a hard, load bearing, smooth material for the femur head and acetabulum which the present invention satisfies.

Certain ceramics have been found to be totally inert in the body, and porous ceramics having a bone size of -200p. have been found to accept the growth of bone tissue so that the ceramic implant may become an integral part of the bone. Since ceramics are brittle in nature and, therefore, have a limitation for prosthetic use, the combination of a structural metallic base material and a ceramic coating appears to present a solution to the problem of achieving extreme strength in a prosthesis while avoiding any toxic effects on the body.

The present invention, in general, provides a method of electrochemically depositing bone particles and collagen onto the external surface of bone prostheses to stimulate bone attachment. Collagen fibrils are dispensed in a gelatin medium by dissolving the gelled collagen in a water-glycerine solution and thereafter adding finely divided bone particles. A voltage applied to a pair of electrodes immersed in the solution causes the formation on the cathode of a bone and collagen coating of from l-5 mils thick.

Accordingly, it is an object of the present invention to provide a method of enhancing bone growth on prostheses by the coating thereof with bone and collagen.

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Another object of this invention is to provide a method of forming prostheses by an electrochemical process wherein bone and collagen are deposited simultaneously in controlled thickness to form a non toxic coating.

A further object of this invention is to provide an improved method of adhering bone particles to a metallic base to form a prosthesis which has the required strength, especially for bone sockets, and is not toxic to the human body.

Other objects, advantages and novel features of the present invention will become apparent from the following description thereof.

Some of the compounds found in the human body can be electrodeposited in a manner similar to the electrodeposition of conventional organic chemicals. For instance, finely divided bone, contained in an organic matrix, can be electrodeposited on various metallic surfaces. The organic matrix enables the transference of bone from the electrolytic medium to the electrode. If it were possible to develop a charge, either cationic or anionic, on virgin bone material, the use of an organic matrix would not be necessary. One commercially available organic matrix or binder, Avitene, is a microcrystalline collagen which is a water insoluble partial acid salt of edible, bovine collagen. Gels produced from it contain a large percentage of particles under one micron in any dimension. The polypeptide collagen morphology and high molecular weight are largely retained in the sub-micron micro-crystals which contain the highly polar groups, NH, NH and OH.

Avitene forms translucent, viscosity-time stable, thixotropic-pseudoplastic gels. High shear is necessary to produce gels. The Waring Blendor and Cowles Dissolver are suitable for low concentrations and sigma blade mixers for high concentrations. Maximum viscosity is obtained at pH 3.0-3.4 At low pH (-2.5), hydrolysis and unwinding of the collagen helix occurs and viscosity decreases; the rate and extent increase with time, temperature and decreasing pH. Above pH 4, gel structure becomes imperfect and collagen fibers begin to coagulate. Salts and ethanol or isopropanol also coacervate gels. Avitene can be made to gel a wide variety of hydrophilic materials including methanol, glycerin, formamide, dimethylsulfoxide, and ethanol or isopropanol/H O solutions up to -40% alcohol/% H O, by weight. Avitene gels of the required concentration have been prepared by attriting fibers in the desired medium for 15-30 minutes in a Waring Blendor (Model 1003) using a lab-scale quantity of 400 grams of Avitene. The concentration should not vary more than i 0.01% for reasonable reproducibility.

In performing the process of the present invention, the Avitene fibers were allowed to soak for Sminutes in the medium'and thereafter were attrited for 2 minutes at a Powerstate (Type 1 16, l 10 volts, Superior Electric Company,) setting of 20, and for 15 minutes minimum at a setting of 60-110 (depending on viscosity) to maintain a controllable vortex. These conditions were applicable to systems having viscosities up to 12,000-16,000 centipoises at room temperature.

During attrition, gel temperature was maintained at -25C by surrounding the jar with a plastic bag partially filled with dry ice, and by reducing or completely stopping agitation when necessary. Sides of the jar were policed at intervals with a rubber spatula to insure thorough attrition. The resultant gel was filtered through a fine, sintered glass filter to remove larger, undispersed fibrils and particle aggregates.

The gel was returned to the Waring Blendor and a varying amount of fine, powdered bone was added. After further agitation, a suspension of finely divided bone, contained in a gel matrix of Avitene, was obtained. The gel proved to be an excellent suspending agent for the finely divided bone.

Initial investigations of several systems at either constant voltage or constant current were carried out in an electrolytic apparatus which consisted of a 500 ml Pyrex glass reaction kettle with cover. Appropriate metal electrodes 2 X 1 0.02 inches were attached by means of a stainless steel clip to A inch stainless steel bars enclosed in glass tubing. Teflon rings were used to seal the steel rods from the glass tubing. 300 ml of solution was utilized and the anode to cathode separation was one inch. A variable dc voltage was applied between the metal electrodes, and the effects of the applied voltage on various aqueous Avitene solutions was observed, recorded and are presented in Table 1.

TABLE 1 following parameters were investigated in the Avitene/- bone electrodeposition:

In the first series of experiments, aqueous Avitene solutions, suitably adjusted to pH 2.8 by the addition of dilute hydrochloric acid, were subject to different applied potentials. Such a series is shown in Table 1, supra. Three different Avitene concentrations were used, and the applied voltage was varied between and 100 volts. It was found that good adhesion to aluminum or stainless steel substrates (cathodes) was achieved when the totalcoating thickness was 4 mils or less. Thicknesses greater than 4 mils resulted in very poor adhesion to the metallic substrate. Of the concentrations investigated, it appeared that a concentration of l.5g Avitene/400g water gave suitable coatings of *3 mils when a potential of 50 volts was applied for 1 minute;

EFFECT OF APPLIED VOLTAGE ON VARIOUS AQUEOUS AVITENE SOLUTIONS Approximate Weight of Applied Deposition Drying of Coating Avitene Voltage Time Coated Thickness g V secs. Cathode Cathode mils. Adhesion 0.75 20 60 Al oven 1 good 0.75 60 Al oven 2 good 0.75 steel oven 2 good 0.75 I00 60 Al oven 4 good 0.75 100 120 Al oven 10 poor 0.75 100 l 20 steel air" l0 poor 1.5 50 60 Al oven 3 good [.5 50 60 steel oven 3 good 1.5 100 60 Al oven 5 fair 1 .5 I00 120 steel oven 8 poor 3.0 50 60 Al oven 6 poor 3.0 50 60 steel air 6 poor 3.0 I00 60 Al oven l0 poor 3.0 100 120 steel oven 15 very poor Each solution contained 400g of water, adjusted to pH 2.8 by addition of dilute hydrochloric acid Oven baked at C for six hours "Air dried for 48 hours The systems were investigated at constant voltage, i.e. current decreasing with electrodeposition time, or constant current, i.e. voltage increasing with time. The

very good adhesion to the cathode was achieved.

In a second series of experiments, four separate solvents were used and the results are shown in Table 2.

TABLE 2 EFFECT OF VARIOUS SOLVENTS ON THE ELECTRODEPOSITION OF AVITENE COLLAGEN Ap roximate Applied Deposition Drying of Coating Solvent Voltage Time Coated Thickness Type V secs. Cathode Cathode mils. Adhesion water 50 60 steel oven 3 good water 50 60 Al oven 3 good water Al oven 8 poor DMSO 50 60 steel ovcn l DMSO 50 I20 steel oven l DMSO" 100 240 Al oven 1 poor DMSO 200 300 steel oven 2 very poor a)DMS0 100 300 steel oven 2 poor 5 ethanol 50 60 steel oven ethanol 50 I20 Al oven ethanol 200 300 Al oven Glycerin/ H 0 50 30 AI oven 2 very good TABLE 2 Continued EFFECT OF VARIOUS SOLVENTS ON THE ELECTRODEPOSITION OF AVITENE COLLAGEN The sohent was adjusted to pH 2.8 by addition of dilute hydrochloric acid. Weight of solvent was 400g, and

weight of Avitene was 1.5g for all samples except (a) which was 3.0g. Oven baked at 70C for six hours Air dried for 48 hours Dimethylsultoxide "(1:1. by Weight) From Table 2 it can be seen that Avitene/dimethylsulfoxide produced solutions which have very poor electrocoating properties; solution conductance was ,low and adhesion to the electrode was very poor. Ethanol produced solutions possessing no electrocoating properties. Aqueous solutions gave rise to reasonable electrocoating properties. The best results were achieved utilizing a solvent mixture of water/glycerin (50/50, by weight). This system had excellent electrocoating properties and the resulting coatings have the best overall adhesion to the metallic substrate. Coatings having thickness of -5 mils were obtained in the latter system by applying a potential difference of 100 volts for 60 seconds.

In a third series of experiments, finely divided bone was added to the optimized Avitene/glycerin/water system prior to electrodeposition. The results are shown in Table 3.

TABLE 3 sion and thickness were achieved utilizing a solution comprised of water/glycerin/Avitene/bone (200/200 1.5/3.0, by weight).

The present invention thus teaches a process by which bone and collagen are simultaneously deposited by electrochemical deposition onto an orthopedic implant to enhance bone repair rates in bone bridge operations. A coating is deposited through a combination of electrophoresis, electrocoagulation, electroosmosis and electrode reactions. Of these, electrophoresis, which involves the movement of charged particles, or ions, dispersed or dissolved in a liquid medium, toward an electrode under the influence of an electric field is considered to be of greatest importance. Colloidal particles carry a large number of unit charges on their surfaces, and each of these particles is thought in the present process to be surrounded by a cloud of counterions. The charge of these particles gives rise to the elec- PARAMETERS lNVESTlGATED IN THE BONE AVlTENE/GLYCERIN SYSTEM A prox. Weight of Weight of Applied Deposition Drying of eating Avitene Bone Voltage Time Coated Thickness g g V secs. Cathode mils. Adhesion L5 1.5 20 oven 1 1.5 1.5 50 oven 1 good 1.5 1.5 50 120 oven 3 good L5 1.5 50 120 air" 3 poor 1.5 3.0, 50 60 oven 2 good 1.5 3.0 60 oven 3 good 1.5 3.0 100 I20 oven 5 good [.5 5.0 100 60 oven 3 poor 1.5 5 .0 100 60 air" 3 poor 1.5 5.0 100 oven 5 poor 1.5 7.0 100 60 oven 7 very poor 1.5 7.0 100 120 oven 10 very poor 1.5 7.0 100 I20 air" 10 very poor Solvent was a 400g solution of glycerin/H O (1:1. by weight). adjusted to pH 2.8 by addition of dilute hydrochloric acid The coated cathode was oven baked at 70C for six hours "Air dried for 48 hours Stainless steel substrate was used in each electrodeposition Four different bone concentrations were investigated. Under the influence of the electric field, bone particles were transported within the organic matrix of the cathode and deposited at this electrode. A bone concentration of 2 parts bone to 1 part of Avitene produced cathode coatings which had good adhesion to the stainless steel substrate. When the concentration exceeded 2 parts bone to 1 part Avitene, thicker coatings were obtained, i.e. for equivalent applied voltage and electrodeposition time, but these had extremely poor adhesion properties. The best coatings for adhetrokinetic or Zeta potential, which is a measure of the electrokinetic charge that surrounds suspended particulate matter. Because of this charge, there is a mutual repulsion of these particles and it is this repulsion which is believed to cause these dispersions to be stable. The charges on the colloidal particles are probably due to a combination of absorbed ions from the solutions, from absorbed surfactant groups, and from the particle itself having ionized groups at the liquidparticle interface. Mobility is affected by the viscosity of the medium, the size, shape and concentration of finishing required to produce a frictionless, freely movable joint. The electrodeposition process also provides for the uniform coverage of irregularly shaped substrates. Because of electrodissolution of the metallic electrode during electrodeposition, improved adhesion properties are realized since the foreign substance is removed.

The electrodeposition process also permits the simultaneous deposition of bone and collagen on an orthopedic implant. This provides for a uniform dispersion of bone and collagen so that when the metallic substrate is removed new bone formation in the damage area is accelerated. The collagen, which isevenly dispersed within the bone implant, promotes healing in connection with the bone portion remaining in the body because of the common fibrous protein in the collagen. Since this fibrous protein is found in connective tissue, bone and cartilage in the body, the body processes do not reject but rather enhance repair of the bone damage. The presence of collagen also increases the rate of normal repair thereby providing for a greater chance of success in bone bridge and other bone operations. The process of the invention is also rapid in relation to normal body processes or other forms of bone repair such as pins, clamps, etc. The process also is exceedingly economical since all the compounds used therein are readily available and no complex equipment is required to make the necessary substrates or form the electrochemical deposition thereon.

Obviously many modifications and variations of the present invention are possible in the light of the above teachings.

What is claimed is: l. A method of forming a prothesis for bone repair or replacement comprising:

electrodepositing finely divided powdered bone particles from aqueous glycerin and collagen dispersions onto a metallic substrate to form the prosthesis as a coating on the substrate; and removing the metallic substrate by dissolution during and after formation of the prosthesis. 2. The method of claim 1 wherein said aqueous glycerin and collagen dispersions comprise translucent, viscosity-time stable, thixotropic pseudoplastic gels having a pH in the range of from 2.5 to 4 for suspending said bone particles.

3. A method of producing an orthopedic implant for enhancing bone repair rates in bone bridge and other bone repair operations comprising:

dispensing collagen fibrils in a gelatin medium formed from the class of hydrophilic materials which includes methanol, glycerin, formamide, dimethylsulfoxide, ethanol solutions of up to substantially 40% alcohol/% water by weight, isopropanol solution of up to substantially 40%/60% water by weight;

dissolving the medium in a water-glycerin solution of 50% water and 50% glycerin by weight; adding finely divided bone particles to the solution; immersing a pair of electrodes one of which is a metallic substrate for a bone prosthesis in the solution; applying a voltage to said electrodes wherein the metallic substrate is the cathode; and forming coatings of bone and collagen on said substrate to a thickness of from 1 to 5 mils. 4. The method of claim 3 wherein said bone particles are dispersed in a gel matrix, I said matrix suspending said particles uniform] throughout said medium. l

5. The method of calim 4 wherein said medium comprises a microcrystalline collagen in the form of a water insoluble partial acid salt of edible bovine collagen,

said gel produced from said medium containing particles substantially less than one micron in any dimension.

6. The method of claim 5 wherein said collagen is a polypeptide collagen having a high molecular weight which is attained by sub-micron micrycrystalline containing highly polar groups such as NH, NH and OH.

7. The method of claim 6 wherein said gel is prepared by attriting collagen fibers in said medium for a period of from 15-30 minutes in a blender;

said fibers allowed to soak for 5 minutes in said medium and thereafter attrited to maintain a controllable vortex.

8. The method of claim 7 wherein the resultant gel is filtered through a sintered glass filter to remove the larger undispersed fibrils and particle aggregates;

a selected amount of powdered bone added tosaid gel,

said gel further agitated so as to obtain a suspension of finely divided bone in the gel matrix of microcrystalline collagen. 

1. A METHOD OF FORMING A PROTHESIS FOR BONE REPAIR OR REPLACEMENT COMPRISING: ELECTRODEPOSITING FINELY DIVIDED POWDERED BONE PARTICLES FROM AQUEOUS GLYCERIN AND COLLAGEN DISPERSIONS ONTO A METALLIC SUBSTRATE TO FORM THE PROSTHESIS AS A COATING ON THE SUBSTRATE, AND REMOVING THE METALLIC SUBSTRATE BY DISSOLUTION DURING AND AFTER FORMATION OF THE PROSTHESIS.
 2. The method of claim 1 wherein said aqueous glycerin and collagen dispersions comprise translucent, viscosity-time stable, thixotropic pseudoplastic gels having a pH in the range of from 2.5 to 4 for suspending said bone particles.
 3. A method of producing an orthopedic implant for enhancing bone repair rates in bone bridge and other bone repair operations comprising: dispensing collagen fibrils in a gelatin medium formed from the class of hydrophilic materials which includes methanol, glycerin, formamide, dimethylsulfoxide, ethanol solutions of up to substantially 40% alcohol/60% water by weight, isopropanol solution of up to substantially 40%/60% water by weight; dissolving the medium in a water-glycerin solution of 50% water and 50% glycerin by weight; adding finely divided bone particles to the solution; immersing a pair of electrodes one of which is a metallic substrate for a bone prosthesis in the solution; applying a voltage to said electrodes wherein the metallic substrate is the cathode; and forming coatings of bone and collagen on said substrate to a thickness of from 1 to 5 mils.
 4. The method of claim 3 wherein said bone particles are dispersed in a gel matrix, said matrix suspending said particles uniformly throughout said medium.
 5. The method of calim 4 wherein said medium comprises a microcrystalline collagen in the form of a water insoluble partial acid salt of edible bovine collagen, said gel produced from said medium containing particles substantially less than one micron in any dimension.
 6. The method of claim 5 wherein said collagen is a polypeptide collagen having a high molecular weight which is attained by sub-micron micrycrystalline containing highly polar groups such as NH, NH2, and OH.
 7. The method of claim 6 wherein said gel is prepared by attriting collagen fibers in said medium for a period of from 15-30 minutes in a blender; said fibers allowed to soak for 5 minutes in said medium and thereafter attrited to maintain a controllable vortex.
 8. The method of claim 7 wherein the resultant gel is filtered through a sintered glass filter to remove the larger undispersed fibrils and particle aggregates; a selected amount of powdered bone added to said gel, said gel further agitated so as to obtain a suspension of finely divided bone in the gel matrix of microcrystalline collagen. 